Malignant tumors (cancers) are the second leading cause of death in the United States, after heart disease (Boring et al., CA Cancer J. Clin. 43:7 (1993)). Cancer is an example of unwanted cell proliferation and is characterized by the increase in the number of abnormal, or neoplastic, cells derived from a normal tissue which proliferate to form a tumor mass or otherwise proliferate unchecked by proper control. Cancer may be further characterized by the invasion of adjacent tissues by these neoplastic tumor cells, and the generation of malignant cells which eventually spread via the blood or lymphatic system to regional lymph nodes and to distant sites via a process called metastasis. In a cancerous state, a cell proliferates under conditions in which normal cells would not grow. Cancer manifests itself in a wide variety of forms, characterized by different degrees of invasiveness and aggressiveness.
Treatments for cancer include resection, radiation therapy and chemotherapeutics. While there are numerous cancer treatments that have been approved for use in humans or that are in various stages of development, many of these treatments are associated with undesired side effects. For example, many cancer treatments do not target tumor or cancer cells specifically, and are often cytotoxic or genotoxic to healthy cells.
One class of chemotherapeutic drug frequently used for treating cancer, alone or in combination with other chemotherapeutics, is the platinum-containing anti-cancer drug class known as “platins.” These drugs include cisplatin, carboplatin and oxaliplatin, which all work by binding to and causing crosslinking of DNA in a cancer cell, ultimately triggering apoptosis. However, drugs like cisplatin are associated with numerous side effects, including nephrotoxicity, neurotoxicity, nausea and vomiting, ototoxicity, electrolyte disturbance, myelotoxicity and hemolytic anemia. In addition, the majority of cancer patients administered platins will eventually relapse with cisplatin-resistant disease. While the exact mechanism for platin-resistance in cancer cells is unclear, some proposed mechanisms include changes in cellular uptake and efflux of the drug, increased detoxification of the drug, inhibition of apoptosis and increased DNA repair. Stordal et al., 2007, IUBMB Life, 59(11):696-99.
There remains a need in the art for improved methods and compositions for treating tumors and cancers.